Pam2CSK4 is a potent agonist of TLR2/TLR6, with an EC50 value of 0.015ng/ml[1]. Pam2CSK4 can activate the platelet nuclear factor-κB and Bruton's tyrosine kinase signaling pathway to promote platelet-endothelial cell interaction[2]. Pam2CSK4 has been widely used as an adjuvant for the development of novel vaccines that can significantly improve the titer of antigen-specific neutralizing antibodies and the persistence of humoral immunity[3].
In vitro, Pam2CSK4 treatment (100ng/ml) of nucleus pulposus (NP) cells isolated from nondegenerative intervertebral discs for 48 hours significantly increased the secretion of several proinflammatory cytokines and chemokines such as IL-6, IL-8, CXCL1, GRO, and CCL2[4]. Treatment of RAW264.7 cells with 100ng/ml Pam2CSK4 for 6 hours significantly promoted the expression of iNOS and stimulated the production of NO[5]. Treatment of peripheral blood mononuclear cells (PBM) with 100ng/ml Pam2CSK4 for 24 hours synergistically enhanced IgG-mediated TNFα production and significantly upregulated Fcγ receptor (FcγR) expression[6].
In vivo, Pam2CSK4 administration via intraperitoneal injection at a dose of 250μg/kg/day for 8 days significantly promoted weight gain and colon length increase during colitis onset and alleviated colitis damage in mice[7].
References:
[1] Irvine K L, Hopkins L J, Gangloff M, et al. The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6[J]. Veterinary research, 2013, 44(1): 50.
[2] Parra-Izquierdo I, Lakshmanan H H S, Melrose A R, et al. The toll-like receptor 2 ligand Pam2CSK4 activates platelet nuclear factor-κB and Bruton’s tyrosine kinase signaling to promote platelet-endothelial cell interactions[J]. Frontiers in Immunology, 2021, 12: 729951.
[3] Qiao Y, Zhan Y, Zhang Y, et al. Pam2CSK4-adjuvanted SARS-CoV-2 RBD nanoparticle vaccine induces robust humoral and cellular immune responses[J]. Frontiers in immunology, 2022, 13: 992062.
[4] Krock E, Rosenzweig D H, Currie J B, et al. Toll-like receptor activation induces degeneration of human intervertebral discs[J]. Scientific reports, 2017, 7(1): 17184.
[5] Kulsantiwong P, Pudla M, Srisaowakarn C, et al. Pam2CSK4 and Pam3CSK4 induce iNOS expression via TBK1 and MyD88 molecules in mouse macrophage cell line RAW264. 7[J]. Inflammation Research, 2017, 66(10): 843-853.
[6] Shah P, Fatehchand K, Patel H, et al. Toll-like receptor 2 ligands regulate monocyte Fcγ receptor expression and function[J]. Journal of Biological Chemistry, 2013, 288(17): 12345-12352.
[7] Wang Y, Han J, Yang G, et al. Therapeutic potential of the secreted Kazal-type serine protease inhibitor SPINK4 in colitis[J]. Nature Communications, 2024, 15(1): 5874.
Pam2CSK4是一种有效的TLR2/TLR6激动剂，EC50值为0.015ng/ml[1]。Pam2CSK4可通过激活血小板核因子κB和Bruton's tyrosine kinase信号通路，促进血小板与内皮细胞的相互作用[2]。Pam2CSK4已广泛用作疫苗佐剂，能显著提升抗原特异性中和抗体滴度及体液免疫的持久性[3]。
在体外，使用100ng/ml的Pam2CSK4处理从非退变椎间盘分离的髓核（NP）细胞48小时，能显著促进多种促炎因子和趋化因子的分泌，包括IL-6、IL-8、CXCL1、GRO和CCL2[4]。用100ng/ml的Pam2CSK4处理RAW264.7细胞6小时，可显著促进iNOS表达并刺激一氧化氮生成[5]。以100ng/ml的Pam2CSK4处理人外周血单核细胞(PBM)24小时，能协同增强IgG介导的TNFα产生，并显著上调Fcγ受体(FcγR)表达[6]。
在体内，通过腹腔注射的方式，以250μg/kg/day的剂量给小鼠连续8天服用 Pam2CSK4，显著促进了结肠炎发作期间小鼠体重的增加和结肠长度的延长，并减轻了结肠炎对小鼠的损伤[7]。